It is the objective of this study to compare mucins secreted by respiratory epithelium of children who have chronic obstructive pulmonary disease (COPD), e.g., cystic fibrosis, bronchial asthma, and asthmatic bronchitis, with mucins secreted by age and sex-matched control subjects. Respiratory tract secretions are usually either inaccessible or grossly contaminated; we have therefore developed an organ culture system for long-term maintenance of human respiratory epithelium and collection of its uncontaminated secretory product. Mucins, electrophoretically and chromatographically similar to those secreted in vivo, can be harvested from culture medium in amounts sufficient to permit fractionation and detailed chemical analysis. Experiments are proposed to refine the culture methodology and thereby insure maximal and consistent mucin secretion. These experiments will be evaluated by histochemical and radioautographic studies, and by quantitation of macromolecules secreted daily into the medium. When optimal culture conditions have been established, explant mucins will be collected, dialyzed, solubilized by reduction and carboxymethylation, and fractionated by standard chromatographic and electrofocusing techniques, or on immuno-absorbent columns containing insolubilized lectins. Carbohydrate and sulfate content, amino acid composition, oligosaccharide structure and linkage to the polypeptide chain, blood group activity, and virus hemagglutinin inhibition activity will be determined for each purified mucin. Chemical analyses of purified mucin(s) secreted in vitro and in vivo will be compared to insure that major alteration of explant mucin has not occurred. If similarity is demonstrated, the composition of purified mucin(s) secreted by explants from normal subjects and subjects with COPD will then be compared. We anticipate that molecular differences will be identified and ultimately related to the underlying pathogenetic mechanism in one or more of these diseases.